SSADH
MCID: SCC001
MIFTS: 45

Succinic Semialdehyde Dehydrogenase Deficiency (SSADH) malady

Neuronal, Metabolic categories

Summaries for Succinic Semialdehyde Dehydrogenase Deficiency

Sources:
8Disease Ontology, 43NIH Rare Diseases, 21Genetics Home Reference, 64Wikipedia, 47OMIM, 19GeneReviews, 33MalaCards
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Genetics Home Reference:21 Succinic semialdehyde dehydrogenase deficiency is a disorder that can cause a variety of neurological problems. People with this condition typically have developmental delay, especially involving speech development; intellectual disability; and decreased muscle tone (hypotonia) soon after birth. About half of those affected experience seizures, difficulty coordinating movements (ataxia), decreased reflexes (hyporeflexia), and behavioral problems. The most common behavioral problems associated with this condition are sleep disturbances, hyperactivity, difficulty maintaining attention, and anxiety. Less frequently, affected individuals may have increased aggression, hallucinations, obsessive-compulsive disorder (OCD), and self-injurious behavior, including biting and head banging. People with this condition can also have problems controlling eye movements. Less common features of succinic semialdehyde dehydrogenase deficiency include uncontrollable movements of the limbs (choreoathetosis), involuntary tensing of the muscles (dystonia), muscle twitches (myoclonus), and a progressive worsening of ataxia.

MalaCards: Succinic Semialdehyde Dehydrogenase Deficiency, also known as 4-hydroxybutyric aciduria, is related to canavan disease and wagr syndrome, and has symptoms including autosomal recessive inheritance, seizures/epilepsy/absences/spasms/status epilepticus and intellectual deficit/mental/psychomotor retardation/learning disability. An important gene associated with Succinic Semialdehyde Dehydrogenase Deficiency is ALDH5A1 (aldehyde dehydrogenase 5 family, member A1), and among its related pathways are Valproic Acid Pathway, Pharmacodynamics and GABA synthesis, release, reuptake and degradation. The compounds L-Aspartic Acid and carboxylate have been mentioned in the context of this disorder. Affiliated tissues include brain and globus pallidus.

Disease Ontology:8 A gamma-amino butyric acid metabolism disorder that is characterized by a deficiency of succinic semialdehyde dehydrogenase resulting in elevated levels of gamma-hydroxybutyric acid.

NIH Rare Diseases:43 Succinic semialdehyde dehydrogenase (ssadh) deficiency is disorder that can cause a variety of neurological and neuromuscular problems. the signs and symptoms can be extremely variable among affected individuals and may include mild to severe intellectual disability; developmental delay (especially involving speech); hypotonia; difficulty coordinating movements (ataxia); and/or seizures. some affected individuals may also have decreased reflexes (hyporeflexia); nystagmus; hyperactivity; and/or behavioral problems. ssadh deficiency is caused by mutations in the aldh5a1 gene and is inherited in an autosomal recessive manner. management is generally symptomatic and typically focuses on treating seizures and neurobehavioral issues. last updated: 9/25/2013

Wikipedia:64 Succinic semialdehyde dehydrogenase deficiency (SSADHD), also known as 4-hydroxybutyric aciduria or... more...

Description from OMIM:47 271980

GeneReviews summary for ssadh

Aliases & Classifications for Succinic Semialdehyde Dehydrogenase Deficiency

Sources:
8Disease Ontology, 9diseasecard, 19GeneReviews, 43NIH Rare Diseases, 20GeneTests, 21Genetics Home Reference, 47OMIM, 10DISEASES, 49Orphanet, 61UMLS, 26ICD10 via Orphanet
See all sources

Classifications:

Malacards categories (disease lists): (See all malacards categories)
Anatomical: Neuronal, Metabolic


Characteristics (Orphanet epidemiological data):

49
succinic semialdehyde dehydrogenase deficiency:
Inheritance: Autosomal recessive; Age of onset: Childhood


Aliases & Descriptions:

succinic semialdehyde dehydrogenase deficiency 8 9 19 43 21 47 10 49 61
4-hydroxybutyric aciduria 8 19 43 21 49
gamma-hydroxybutyric aciduria 8 19 21
ssadh deficiency 19 43 21
succinic semialdehyde dehydrogenase 9 20
gamma-hydroxybutyric acidemia 21
gamma-hydroxybutyricaciduria 43
4-hydroxybutyricaciduria 21
gaba metabolic defect 43
ssadh 8


External Ids:

Disease Ontology8 DOID:0060175
OMIM47 271980
ICD10 via Orphanet26 E72.8

Related Diseases for Succinic Semialdehyde Dehydrogenase Deficiency

Sources:
17GeneCards, 18GeneDecks
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Diseases related to Succinic Semialdehyde Dehydrogenase Deficiency via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show all 21)
idRelated DiseaseScoreTop Affiliating Genes
1canavan disease30.5ASPA
2wagr syndrome30.5WT1
3mental retardation30.5WT1, ASPA, ALDH5A1
4decr deficiency10.5
5juvenile absence epilepsy10.4
6neuroleptic malignant syndrome10.4
7n syndrome10.4
8sleep disorder10.4
9char syndrome10.4
10hypotonia10.4
11seizure disorder10.4
12status epilepticus10.3
13williams syndrome10.3
14dysequilibrium syndrome10.2
15photosensitive epilepsy10.0
16homocarnosinosis10.0ALDH5A1, ABAT
17pancreatitis10.0ALDH9A1
18epilepsy syndrome10.0GLUD1, ABAT, ASPA, ALDH5A1
19liver cirrhosis10.0GPT, ALDH9A1
20alcoholic liver cirrhosis10.0ALDH9A1, GPT
21metabolic syndrome x10.0GLUD1, ALDH9A1, ALDH5A1

Graphical network of the top 20 diseases related to Succinic Semialdehyde Dehydrogenase Deficiency:



Diseases related to succinic semialdehyde dehydrogenase deficiency

Clinical Features for Succinic Semialdehyde Dehydrogenase Deficiency

Sources:
47OMIM, 49Orphanet
See all sources

Clinical features from OMIM:

271980

Clinical synopsis from OMIM:

271980

Symptoms:

49 (show all 7)
  • autosomal recessive inheritance
  • seizures/epilepsy/absences/spasms/status epilepticus
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • ataxia/incoordination/trouble of the equilibrium
  • hypotonia
  • psychic/behavioural troubles
  • organic acid metabolism anomalies

Drugs & Therapeutics for Succinic Semialdehyde Dehydrogenase Deficiency

Sources:
5CenterWatch, 42NIH Clinical Center, 6ClinicalTrials
See all sources

Approved drugs:

Search CenterWatch for Succinic Semialdehyde Dehydrogenase Deficiency

Drug clinical trials:

Search ClinicalTrials for Succinic Semialdehyde Dehydrogenase Deficiency

Search NIH Clinical Center for Succinic Semialdehyde Dehydrogenase Deficiency

Search CenterWatch for Succinic Semialdehyde Dehydrogenase Deficiency

Genetic Tests for Succinic Semialdehyde Dehydrogenase Deficiency

Sources:
20GeneTests
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Genetic tests related to Succinic Semialdehyde Dehydrogenase Deficiency:

id Genetic test Affiliating Genes
1 Succinic Semialdehyde Dehydrogenase Deficiency20 ALDH5A1

Anatomical Context for Succinic Semialdehyde Dehydrogenase Deficiency

Sources:
33MalaCards
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MalaCards organs/tissues related to Succinic Semialdehyde Dehydrogenase Deficiency:

33
Brain, Globus pallidus

Animal Models for Succinic Semialdehyde Dehydrogenase Deficiency or affiliated genes

Sources:
28inGenious Targeting Laboratory
See all sources

Publications for Succinic Semialdehyde Dehydrogenase Deficiency

Sources:
51PubMed
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Articles related to Succinic Semialdehyde Dehydrogenase Deficiency:

(show top 50)    (show all 62)
idTitleAuthorsYear
1
Therapeutic efficacy of magnesium valproate in succinic semialdehyde dehydrogenase deficiency. (23430529)
2013
2
Thirty years beyond discovery--clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. (22739941)
2013
3
Succinic semialdehyde dehydrogenase deficiency: an inheritable neurometabolic disease]. (23516105)
2013
4
A novel ALDH5A1 mutation is associated with succinic semialdehyde dehydrogenase deficiency and severe intellectual disability in an Iranian family. (23825041)
2013
5
Efficacy of vigabatrin intervention in a mild phenotypic expression of succinic semialdehyde dehydrogenase deficiency. (23430864)
2012
6
A novel ALDH5A1 mutation in a patient with succinic semialdehyde dehydrogenase deficiency. (22437753)
2012
7
A boy with a severe phenotype of succinic semialdehyde dehydrogenase deficiency. (21612881)
2012
8
Epilepsy in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. (21664777)
2011
9
Neuropathology in succinic semialdehyde dehydrogenase deficiency. (20304328)
2010
10
Cerebellar atrophy in human and murine succinic semialdehyde dehydrogenase deficiency. (20445195)
2010
11
Sleep disorders in succinic semialdehyde dehydrogenase deficiency: a family report. (19896403)
2010
12
Head bobbing due to succinic semialdehyde dehydrogenase deficiency. (20548048)
2010
13
Succinic semialdehyde dehydrogenase deficiency: decrease in 4-OH-butyric acid levels with low doses of vigabatrin]. (20018576)
2010
14
Decreased GABA-A binding on FMZ-PET in succinic semialdehyde dehydrogenase deficiency. (19667317)
2009
15
Sensory integration intervention: historical concepts, treatment strategies and clinical experiences in three patients with succinic semialdehyde dehydrogenase (SSADH) deficiency. (19381864)
2009
16
Succinic semialdehyde dehydrogenase deficiency: lessons from mice and men. (19172412)
2009
17
Polysomnographic abnormalities in succinic semialdehyde dehydrogenase (SSADH) deficiency. (20041601)
2009
18
Circadian distribution of generalized tonic-clonic seizures associated with murine succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. (18514581)
2008
19
'Succinic semialdehyde dehydrogenase deficiency: phenotype evolution in an adolescent patient at 20-year follow-up'. (18811705)
2008
20
Neuropsychiatric morbidity in adolescent and adult succinic semialdehyde dehydrogenase deficiency patients. (18622364)
2008
21
Vigabatrin improves paroxysmal dystonia in succinic semialdehyde dehydrogenase deficiency. (17438226)
2007
22
Enzymatic and metabolic evidence for a region specific mitochondrial dysfunction in brains of murine succinic semialdehyde dehydrogenase deficiency (Aldh5a1-/- mice). (17303287)
2007
23
Succinic semialdehyde dehydrogenase deficiency: GABAB receptor-mediated function. (16647690)
2006
24
Photosensitive absence epilepsy with myoclonias and heterozygosity for succinic semialdehyde dehydrogenase (SSADH) deficiency. (15134710)
2004
25
The molecular basis of succinic semialdehyde dehydrogenase deficiency in one family. (15059623)
2004
26
Succinic semialdehyde dehydrogenase deficiency (SSADH) (4-hydroxybutyric aciduria, gamma-hydroxybutyric aciduria). (15341910)
2004
27
Neurodevelopmental pattern of succinic semialdehyde dehydrogenase deficiency (gamma-hydroxybutyric aciduria). (15287248)
2004
28
Effect of valproic acid on the urinary metabolic profile of a patient with succinic semialdehyde dehydrogenase deficiency. (12829002)
2003
29
Clinical spectrum of succinic semialdehyde dehydrogenase deficiency. (12743223)
2003
30
Vigabatrin and newer interventions in succinic semialdehyde dehydrogenase deficiency. (12891656)
2003
31
Succinic semialdehyde dehydrogenase deficiency in children and adults. (12891657)
2003
32
Monitoring of 4-hydroxybutyric acid levels in body fluids during vigabatrin treatment in succinic semialdehyde dehydrogenase deficiency. (14595661)
2003
33
Rapid and sensitive detection of urinary 4-hydroxybutyric acid and its related compounds by gas chromatography-mass spectrometry in a patient with succinic semialdehyde dehydrogenase deficiency. (12127325)
2002
34
Selective involvement of the globus pallidus and dentate nucleus in succinic semialdehyde dehydrogenase deficiency. (12136353)
2002
35
Neuroleptic malignant syndrome in a patient with succinic semialdehyde dehydrogenase deficiency. (11819156)
2002
36
Mutation analysis in a patient with succinic semialdehyde dehydrogenase deficiency: a compound heterozygote with 103-121del and 1460T>A of the ALDH5A1 gene. (11901270)
2002
37
Prenatal diagnosis of succinic semialdehyde dehydrogenase deficiency: increased accuracy employing DNA, enzyme, and metabolite analyses. (11243727)
2001
38
MRI findings in succinic semialdehyde dehydrogenase deficiency. (10774997)
2000
39
Succinic semialdehyde dehydrogenase deficiency in siblings: clinical heterogeneity and response to early treatment. (10234622)
1999
40
4-Hydroxybutyric acid and the clinical phenotype of succinic semialdehyde dehydrogenase deficiency, an inborn error of GABA metabolism. (9553943)
1998
41
Unusual enzyme findings in five patients with metabolic profiles suggestive of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria). (9686370)
1998
42
Seizures in a boy with succinic semialdehyde dehydrogenase deficiency treated with vigabatrin (gamma-vinyl-GABA). (8803774)
1996
43
Pre- and postnatal diagnosis of succinic semialdehyde dehydrogenase deficiency using enzyme and metabolite assays. (7707697)
1994
44
Prenatal detection of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria) (8464836)
1993
45
Succinic Semialdehyde Dehydrogenase Deficiency (20301374)
1993
46
Succinic semialdehyde dehydrogenase deficiency associated with combined 4-hydroxybutyric and dicarboxylic acidurias: potential for clinical misdiagnosis based on urinary organic acid profiling. (2926573)
1989
47
Urinary organic acids in succinic semialdehyde dehydrogenase deficiency: evidence of alpha-oxidation of 4-hydroxybutyric acid, interaction of succinic semialdehyde with pyruvate dehydrogenase and possible secondary inhibition of mitochondrial beta-oxidation. (3126356)
1987
48
Succinic semialdehyde dehydrogenase deficiency--a further case. (2433500)
1985
49
Succinic semialdehyde dehydrogenase deficiency. (6536727)
1984
50
Succinic semialdehyde dehydrogenase deficiency: an inborn error of gamma-aminobutyric acid metabolism. (6627675)
1983

Genetic Variations for Succinic Semialdehyde Dehydrogenase Deficiency

Sources:
63UniProtKB/Swiss-Prot
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Genetic disease variations for Succinic Semialdehyde Dehydrogenase Deficiency:

63 (show all 12)
id Symbol AA change Variation SNP ID
1ALDH5A1p.Cys93PheVAR_026199
2ALDH5A1p.Gly176ArgVAR_026200
3ALDH5A1p.Cys223TyrVAR_026201
4ALDH5A1p.Thr233MetVAR_026202
5ALDH5A1p.Asn255SerVAR_026203
6ALDH5A1p.Gly268GluVAR_026204
7ALDH5A1p.Asn335LysVAR_026205
8ALDH5A1p.Pro382LeuVAR_026206
9ALDH5A1p.Pro382GlnVAR_026207
10ALDH5A1p.Gly409AspVAR_026208
11ALDH5A1p.Val487GluVAR_026209
12ALDH5A1p.Gly533ArgVAR_026210

Expression for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

Sources:
1BioGPS, 15Gene Expression Omnibus DataSets
See all sources
Expression patterns in normal tissues for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

Search GEO for disease gene expression data for Succinic Semialdehyde Dehydrogenase Deficiency.

Pathways for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

Sources:
50PharmGKB, 54Reactome, 12EMD Millipore, 30KEGG, 38NCBI BioSystems Database
See all sources

Pathways related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards/GeneDecks:

(show all 16)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.9ALDH5A1, ABAT
2
Hide members
9.9ALDH5A1, ABAT
39.7ALDH9A1, ABAT
4
Hide members
9.6ALDH9A1, ALDH6A1
5
Hide members
9.5ABAT, ALDH6A1, ALDH5A1
69.4GLUD1, GPT
79.3ASPA, ABAT, GPT
8
Hide members
9.1ALDH1B1, ALDH9A1
99.1ALDH9A1, ALDH1B1
10
Tyrosine metabolism p.1 (dopamine)
Hide members
9.1ALDH9A1, ALDH1B1
118.8ASPA, ALDH1B1, ALDH9A1
128.5ALDH9A1, ALDH6A1, ALDH1B1, ABAT
13
Hide members
8.2ALDH9A1, ALDH1B1, ALDH4A1, GLUD1
148.1ALDH5A1, ALDH4A1, ASPA, ABAT, GPT, GLUD1
158.0GLUD1, GPT, ALDH4A1, ALDH6A1, ALDH9A1
16
Hide members
7.0GPT, ABAT, ALDH4A1, ALDH1B1, ALDH6A1, ALDH9A1

Compounds for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

Sources:
11DrugBank, 24HMDB, 45Novoseek, 29IUPHAR, 60Tocris Bioscience, 50PharmGKB, 2BitterDB
See all sources

Compounds related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards/GeneDecks:

(show all 46)
idCompoundScoreTop Affiliating Genes
1L-Aspartic Acid11 2411.0ASPA, GLUD1
2carboxylate4510.0ABAT, ASPA
3succinic semialdehyde4510.0ALDH5A1, ABAT, AKR7A2
4vigabatrin45 29 1111.9GLUD1, ABAT, ALDH5A1
5aminooxyacetic acid45 2910.9GPT, ABAT
6taurine45 60 2411.9ABAT, WT1
7succinate459.9ALDH5A1, ABAT, GLUD1
8phenelzine45 1110.9GPT, ABAT
9monoethylglycinexylidide459.8GLUD1, GPT
10l-alanine29 60 11 2412.8GPT, ABAT
11nadp+459.7GLUD1, ALDH9A1
125-hydroxytryptophol459.7ALDH9A1, GPT
13thymol45 2910.7ALDH9A1, GPT
14trichloroethylene459.6ALDH9A1, GPT
15ornithine45 2410.6ABAT, GLUD1, WT1
16valproic acid45 50 11 2412.6ALDH5A1, ABAT, GPT
17nad+459.6GLUD1, ALDH9A1, ALDH5A1
18glutaraldehyde459.6GLUD1, ALDH9A1
19aldose459.6ALDH9A1, AKR7A2
20vitamin b6459.6ALDH5A1, ABAT
21gamma-hydroxybutyrate459.6AKR7A2, GLUD1, ABAT, ALDH5A1
22Nicotinamide-Adenine-Dinucleotide119.5ALDH9A1, GLUD1
23valproate459.5GLUD1, GPT, ABAT
24pyridoxal 5-phosphate459.5GLUD1, GPT, ABAT
25gsts459.5AKR7A2, ALDH9A1
26perillic acid45 2410.5ALDH9A1, ALDH1B1
27methylmalonic acid45 2410.4ALDH1B1, ALDH9A1
285-hydroxyindoleacetic acid45 2410.4ALDH9A1, ALDH1B1
29gaba459.4GLUD1, ABAT, ALDH9A1, ALDH5A1
30alpha-ketoglutarate459.3ALDH5A1, ABAT, GPT, GLUD1
31acetyl-coa45 2410.3ALDH9A1, ALDH6A1, ASPA, GLUD1
32beta-alanine45 60 11 2412.2ALDH9A1, ALDH1B1, ABAT
33acetic acid45 29 11 2412.2ASPA, ALDH1B1, ALDH9A1
34choline45 11 2411.2ALDH9A1, GPT, GLUD1
35pyruvate459.1ALDH9A1, GPT, GLUD1
36famotidine45 2 11 2412.0ALDH4A1, ABAT, GPT, GLUD1
37l-glutamic acid29 11 2411.0GLUD1, GPT, ABAT, ALDH4A1
38(S)-Methylmalonic acid semialdehyde248.9ALDH9A1, ALDH6A1, ALDH1B1, ABAT
39glutamine458.8ALDH5A1, ABAT, GPT, GLUD1, WT1
40aspartate458.7GLUD1, GPT, ABAT, ASPA, ALDH9A1
41alanine458.7GLUD1, GPT, ABAT, ALDH9A1, ALDH5A1
42ethanol45 50 11 2411.6ALDH9A1, ALDH1B1, ABAT, GPT
43nadph45 249.3GLUD1, ABAT, ALDH4A1, ALDH1B1, ALDH9A1
44nad29 249.0GLUD1, ALDH4A1, ALDH1B1, ALDH6A1, ALDH9A1, ALDH5A1
45nadh45 11 2410.0GLUD1, ALDH4A1, ALDH1B1, ALDH6A1, ALDH9A1, ALDH5A1
46glutamate458.0GLUD1, GPT, ABAT, ASPA, ALDH4A1, ALDH9A1

GO Terms for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

Sources:
16Gene Ontology
See all sources

Cellular components related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1mitochondrionGO:0057397.8ABAT, ALDH1B1, ALDH6A1, ALDH9A1, ALDH5A1, GLUD1
2mitochondrial matrixGO:0057597.5ALDH5A1, ALDH6A1, ALDH1B1, ALDH4A1, ABAT, GLUD1

Biological processes related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards/GeneDecks:

(show all 7)
idNameGO IDScoreTop Affiliating Genes
1gamma-aminobutyric acid catabolic processGO:00945010.0ABAT, ALDH5A1
2neurotransmitter catabolic processGO:04213510.0ALDH5A1, ABAT
3glutamine metabolic processGO:0065419.7ALDH5A1, GLUD1
4cellular aldehyde metabolic processGO:0060819.6AKR7A2, ALDH9A1
5cellular amino acid biosynthetic processGO:0086529.1GPT, GLUD1
6cellular nitrogen compound metabolic processGO:0346418.2ALDH9A1, ALDH6A1, ALDH4A1, GPT, GLUD1
7small molecule metabolic processGO:0442818.0GPT, ALDH4A1, ALDH6A1, ALDH9A1, GLUD1

Molecular functions related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1aldehyde dehydrogenase (NAD) activityGO:0040298.6ALDH9A1, ALDH1B1, ALDH4A1

Products for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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Sources for Succinic Semialdehyde Dehydrogenase Deficiency

3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
29IUPHAR
30KEGG
35MeSH
36MESH via Orphanet
37MGI
40NCIt
41NDF-RT
44NINDS
45Novoseek
47OMIM
48OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
61UMLS
62UMLS via Orphanet